ABSTRACT Darkfield imaging enables detection of unlabeled materials in tissues. The system we are requesting, a CytoViva Hyperspectral Microscopy system, combines proprietary darkfield microscope optics with hyperspectral detection to allow imaging, mapping and characterization of nanoscale materials (particles, viruses, bacteria) in tissues and cells. Darkfield imaging that is coupled with hyperspectral imaging, allows verification of the object through a characteristic spectral profile. The proprietary condenser increases the resolution over standard darkfield. The hyperspectral aspect of this system can also be used to understand histologic staining co- localization. Over the past 10 years, the UC Davis Cellular and Molecular Imaging Core (CAMI) has combined excellence in microscopy and fluorescence with complete sample preparation capabilities to serve over 90 UC Davis user laboratories. This is an established, shared facility resource that is supported with a fee for use (re-charge). The capabilities of the CytoViva system are needed by the co-investigators on this application. These major and minor users will use this instrument to study how nanomaterials interact with tissues and cells, to monitor bioavailability and composition of nanotherapeutics, to study the biology of inflammatory cells and to understand subtle shifts in toxicologic pathology and pathogen responses. This instrument does not duplicate existing instrumentation on our campus. Additional capability that will be supplied with this instrument includes fluorescence to allow colocalization of fluorescent signals with the hyperspectral image as is required by our users. The robust image analysis software included with this system allows spectral identification of nanoscale objects in a wide range of environments based on wavelength, scatter intensity, and scatter spatial properties. Most importantly, the image analysis software enables identification of nanoscale objects in the spectral image based on peak wavelength allowing standard histologic approaches to be used. This provides an important intermediate analysis capability as an alternative to EM or Raman spectroscopy for sample analysis and offers significant benefits to users in terms of lower cost and faster throughput. CAMI staff will provide training and consulting on imaging projects involving the CytoViva system and placement of this instrument in our core facility is a logical complement to our current capabilities which include excellence in sample preparation. This equipment will increase the impact of NIH funded research at UC Davis.